612 research outputs found

    Community Smells -- The Sources of Social Debt: A Systematic Literature Review

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    Context: Social debt describes the accumulation of unforeseen project costs (or potential costs) from sub-optimal software development processes. Community smells are sociotechnical anti-patterns and one source of social debt that impact software teams, development processes, outcomes, and organizations. Objective: To provide an overview of community smells based on published literature, and describe future research. Method: We conducted a systematic literature review (SLR) to identify properties, understand origins and evolution, and describe the emergence of community smells. This SLR explains the impact of community smells on teamwork and team performance. Results: We include 25 studies. Social debt describes the impacts of poor socio-technical decisions on work environments, people, software products, and society. For each of the 30 identified community smells, we provide a description, management approaches, organizational strategies, and mitigation effectiveness. We identify five groups of management approaches: organizational strategies, frameworks, models, tools, and guidelines. We describe 11 properties of community smells. We develop the Community Smell Stages Framework to concisely describe the origin and evolution of community smells. We describe the causes and effects for each community smell. We identify and describe 8 types of causes and 11 types of effects for community smells. Finally, we provide 8 Sankey diagrams that offer insights into threats the community smells pose to teamwork factors and team performance. Conclusion: Community smells explain the influence work conditions have on software developers. The literature is scarce and focuses on a small number of community smells. Thus, community smells still need more research. This review organizes the state of the art about community smells and provides motivation for future research along with educational material.Comment: Accepted for publication in Information and Software Technolog

    Precision and manufacturing at the Lawrence Livermore National Laboratory

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    Precision Engineering is one of the Lawrence Livermore National Laboratory's core strengths. This paper discusses the past and present current technology transfer efforts of LLNL's Precision Engineering program and the Livermore Center for Advanced Manufacturing and Productivity (LCAMP). More than a year ago the Precision Machine Commercialization project embodied several successful methods of transferring high technology from the National Laboratories to industry. Currently, LCAMP has already demonstrated successful technology transfer and is involved in a broad spectrum of current programs. In addition, this paper discusses other technologies ripe for future transition including the Large Optics Diamond Turning Machine

    Micronutrient Adequacy in Preschool Children Attending Family Child Care Homes

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    Limited data is available on the micronutrient intake and adequacy in preschool children enrolled in family child care homes (FCCH). The goal of this paper is to describe the micronutrient adequacy relative to age-specific recommendations of preschool-aged children (aged 2–5 years) attending FCCH in Rhode Island (RI). Dietary data among younger preschoolers (aged 2–3 years), n = 245) and older preschoolers (aged 4–5 years), n = 121) in 118 RI FCCH (N = 366 children) were analyzed. Nutrient adequacy was assessed as the amount of nutrient per 1000 kcal of the diet that would meet the Institute of Medicine nutrient requirements (critical nutrient density), and it was compared to the observed nutrient densities of the children. The sodium:potassium ratio was also calculated. For most micronutrients, the observed density met or exceeded the recommendation, meaning the children’s intake was adequate. However, a high proportion of children had nutrient densities under the recommendation for vitamins D, E, K, and potassium (86.1%, 89.1%, 70.8%, and 99.2% of children, respectively). The mean vitamin B12, potassium, and zinc densities were statistically higher in younger vs. older preschoolers (p \u3c 0.05 for all). Low densities in calcium and vitamins K and B5 were more frequent in older children vs. younger children (p \u3c 0.05). In addition, older preschoolers had a higher sodium:potassium ratio than younger children (p \u3c 0.05). The micronutrient intake density was adequate for most nutrients. However, intake of some nutrients was of concern. Further attention to training and compliance in FCCH may improve the diet quality of those cared for in these settings

    Cellular responses to modified Plasmodium falciparum MSP119 antigens in individuals previously exposed to natural malaria infection

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    <p>Abstract</p> <p>Background</p> <p>MSP1 processing-inhibitory antibodies bind to epitopes on the 19 kDa C-terminal region of the <it>Plasmodium falciparum </it>merozoite surface protein 1 (MSP1<sub>19</sub>), inhibiting erythrocyte invasion. Blocking antibodies also bind to this antigen but prevent inhibitory antibodies binding, allowing invasion to proceed. Recombinant MSP1<sub>19 </sub>had been modified previously to allow inhibitory but not blocking antibodies to continue to bind. Immunization with these modified proteins, therefore, has the potential to induce more effective protective antibodies. However, it was unclear whether the modification of MSP1<sub>19 </sub>would affect critical T-cell responses to epitopes in this antigen.</p> <p>Methods</p> <p>The cellular responses to wild-type MSP1<sub>19 </sub>and a panel of modified MSP1<sub>19 </sub>antigens were measured using an <it>in-vitro </it>assay for two groups of individuals: the first were malaria-naΓ―ve and the second had been naturally exposed to <it>Plasmodium falciparum </it>infection. The cellular responses to the modified proteins were examined using cells from malaria-exposed infants and adults.</p> <p>Results</p> <p>Interestingly, stimulation indices (SI) for responses induced by some of the modified proteins were at least two-fold higher than those elicited by the wild-type MSP1<sub>19</sub>. A protein with four amino acid substitutions (Glu27β†’Tyr, Leu31β†’Arg, Tyr34β†’Ser and Glu43β†’Leu) had the highest stimulation index (SI up to 360) and induced large responses in 64% of the samples that had significant cellular responses to the modified proteins.</p> <p>Conclusion</p> <p>This study suggests that specific MSP1<sub>19 </sub>variants that have been engineered to improve their antigenicity for inhibitory antibodies, retain T-cell epitopes and the ability to induce cellular responses. These proteins are candidates for the development of MSP1-based malaria vaccines.</p

    Modernizing and Expanding the NASA Space Geodesy Network to Meet Future Geodetic Requirements

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    NASA maintains and operates a global network of Very Long Baseline Interferometry (VLBI), Satellite Laser Ranging (SLR), and Global Navigation Satellite System ground stations as part of the NASA Space Geodesy Program. The NASA Space Geodesy Network (NSGN) provides the geodetic products that support Earth observations and the related science requirements as outlined by the US National Research Council (NRC in Precise geodetic infrastructure: national requirements for a shared resource, National Academies Press, Washington, 2010. http://nap.edu/12954, Thriving on our changing planet: a decadal strategy for Earth observation from space, National Academies Press, Washington, 2018. http://nap.edu/24938). The Global Geodetic Observing System (GGOS) and the NRC have set an ambitious goal of improving the Terrestrial Reference Frame to have an accuracy of 1 mm and stability of 0.1 mm per year, an order of magnitude beyond current capabilities. NASA and its partners within GGOS are addressing this challenge by planning and implementing modern geodetic stations colocated at existing and new sites around the world. In 2013, NASA demonstrated the performance of its next-generation systems at the prototype next-generation core site at NASAs Goddard Geophysical and Astronomical Observatory in Greenbelt, Maryland. Implementation of a new broadband VLBI station in Hawaii was completed in 2016. NASA is currently implementing new VLBI and SLR stations in Texas and is planning the replacement of its other aging domestic and international legacy stations. In this article, we describe critical gaps in the current global network and discuss how the new NSGN will expand the global geodetic coverage and ultimately improve the geodetic products. We also describe the characteristics of a modern NSGN site and the capabilities of the next-generation NASA SLR and VLBI systems. Finally, we outline the plans for efficiently operating the NSGN by centralizing and automating the operations of the new geodetic stations

    Phase 1 Study of Two Merozoite Surface Protein 1 (MSP1(42)) Vaccines for Plasmodium falciparum Malaria

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    OBJECTIVES: To assess the safety and immunogenicity of two vaccines, MSP1(42)-FVO/Alhydrogel and MSP1(42)-3D7/Alhydrogel, targeting blood-stage Plasmodium falciparum parasites. DESIGN: A Phase 1 open-label, dose-escalating study. SETTING: Quintiles Phase 1 Services, Lenexa, Kansas between July 2004 and November 2005. PARTICIPANTS: Sixty healthy malaria-naΓ―ve volunteers 18–48 y of age. INTERVENTIONS: The C-terminal 42-kDa region of merozoite surface protein 1 (MSP1(42)) corresponding to the two allelic forms present in FVO and 3D7 P. falciparum lines were expressed in Escherichia coli, refolded, purified, and formulated on Alhydrogel (aluminum hydroxide). For each vaccine, volunteers in each of three dose cohorts (5, 20, and 80 ΞΌg) were vaccinated at 0, 28, and 180 d. Volunteers were followed for 1 y. OUTCOME MEASURES: The safety of MSP1(42)-FVO/Alhydrogel and MSP1(42)-3D7/Alhydrogel was assessed. The antibody response to each vaccine was measured by reactivity to homologous and heterologous MSP1(42), MSP1(19), and MSP1(33) recombinant proteins and recognition of FVO and 3D7 parasites. RESULTS: Anti-MSP1(42) antibodies were detected by ELISA in 20/27 (74%) and 22/27 (81%) volunteers receiving three vaccinations of MSP1(42)-FVO/Alhydrogel or MSP1(42)-3D7/Alhydrogel, respectively. Regardless of the vaccine, the antibodies were cross-reactive to both MSP1(42)-FVO and MSP1(42)-3D7 proteins. The majority of the antibody response targeted the C-terminal 19-kDa domain of MSP1(42), although low-level antibodies to the N-terminal 33-kDa domain of MSP1(42) were also detected. Immunofluorescence microscopy of sera from the volunteers demonstrated reactivity with both FVO and 3D7 P. falciparum schizonts and free merozoites. Minimal in vitro growth inhibition of FVO or 3D7 parasites by purified IgG from the sera of the vaccinees was observed. CONCLUSIONS: The MSP1(42)/Alhydrogel vaccines were safe and well tolerated but not sufficiently immunogenic to generate a biologic effect in vitro. Addition of immunostimulants to the Alhydrogel formulation to elicit higher vaccine-induced responses in humans may be required for an effective vaccine

    A novel malaria vaccine candidate antigen expressed in Tetrahymena thermophila

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    Development of effective malaria vaccines is hampered by the problem of producing correctly folded Plasmodium proteins for use as vaccine components. We have investigated the use of a novel ciliate expression system, Tetrahymena thermophila, as a P. falciparum vaccine antigen platform. A synthetic vaccine antigen composed of N-terminal and C-terminal regions of merozoite surface protein-1 (MSP-1) was expressed in Tetrahymena thermophila. The recombinant antigen was secreted into the culture medium and purified by monoclonal antibody (mAb) affinity chromatography. The vaccine was immunogenic in MF1 mice, eliciting high antibody titers against both N- and C-terminal components. Sera from immunized animals reacted strongly with P. falciparum parasites from three antigenically different strains by immunofluorescence assays, confirming that the antibodies produced are able to recognize parasite antigens in their native form. Epitope mapping of serum reactivity with a peptide library derived from all three MSP-1 Block 2 serotypes confirmed that the MSP-1 Block 2 hybrid component of the vaccine had effectively targeted all three serotypes of this polymorphic region of MSP-1. This study has successfully demonstrated the use of Tetrahymena thermophila as a recombinant protein expression platform for the production of malaria vaccine antigens

    A Pair of Dopamine Neurons Target the D1-Like Dopamine Receptor DopR in the Central Complex to Promote Ethanol-Stimulated Locomotion in Drosophila

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    Dopamine is a mediator of the stimulant properties of drugs of abuse, including ethanol, in mammals and in the fruit fly Drosophila. The neural substrates for the stimulant actions of ethanol in flies are not known. We show that a subset of dopamine neurons and their targets, through the action of the D1-like dopamine receptor DopR, promote locomotor activation in response to acute ethanol exposure. A bilateral pair of dopaminergic neurons in the fly brain mediates the enhanced locomotor activity induced by ethanol exposure, and promotes locomotion when directly activated. These neurons project to the central complex ellipsoid body, a structure implicated in regulating motor behaviors. Ellipsoid body neurons are required for ethanol-induced locomotor activity and they express DopR. Elimination of DopR blunts the locomotor activating effects of ethanol, and this behavior can be restored by selective expression of DopR in the ellipsoid body. These data tie the activity of defined dopamine neurons to D1-like DopR-expressing neurons to form a neural circuit that governs acute responding to ethanol
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